Expert opinions on implementation of MDMA-assisted therapy in Europe: critical appraisal towards training, clinical practice, and regulation.

Introduction: The positive results of MDMA from Phase 2 and 3 clinical trials in MDMA-assisted therapy (MDMA-AT) for the treatment of post-traumatic stress disorder (PTSD) call for a critical evaluation of its regulatory status within the European mental healthcare system. This is driven by the recent submission of MDMA-AT for FDA approval in the United States. Unless coordinated efforts in the European regulatory landscape start, there may be potential divergences in national regulatory strategies. Gaining insights from researchers and clinicians involved in the application of MDMA-AT may be useful in guiding the discussion of factors involved in its implementation.Method: A comprehensive invitation-only survey was sent to researchers and clinicians involved in MDMA-AT clinical trials and contributors to the scientific literature on MDMA-AT from around the globe. This study aimed to collect opinions on clinical practices, training, and regulation worldwide, examining the global best practices and pitfalls to outline strategies for possible European implementation of MDMA-AT.Results: The survey, which included responses from 68 experts, yielded a range of opinions where a large majority endorsed the need for training and standardization, emphasizing equity and access, stressing impediments in the national approval processes, and reflecting critically on anticipated spill-over effects of MDMA-AT in clinical settings.Conclusion: The experts highlight the need for science-informed policy development, active regulatory involvement, and international cooperation to incorporate MDMA-AT into the European mental healthcare system in general and the treatment of PTSD in particular. The study emphasizes the importance of ongoing research, open professional discourse, and collaborative engagement to facilitate MDMA-AT's ethical and effective implementation.

Positive clinical trials of therapy using MDMA for treating post-traumatic stress disorder (PTSD) call for a thorough review of its regulatory status in Europe, especially following its submission for approval in the United States.A global survey of 68 researchers and clinicians underscores the necessity for standardized training, equitable access, and streamlined national approval processes for MDMA therapy, highlighting potential clinical benefits and challenges.Experts emphasize the importance of science-based policies, international cooperation, and continuous research to effectively integrate MDMA therapy into European mental healthcare for PTSD treatment.

Subjective evidence evaluation survey for many-analysts studies.

Many-analysts studies explore how well an empirical claim withstands plausible alternative analyses of the same dataset by multiple, independent analysis teams. Conclusions from these studies typically rely on a single outcome metric (e.g. effect size) provided by each analysis team. Although informative about the range of plausible effects in a dataset, a single effect size from each team does not provide a complete, nuanced understanding of how analysis choices are related to the outcome. We used the Delphi consensus technique with input from 37 experts to develop an 18-item subjective evidence evaluation survey (SEES) to evaluate how each analysis team views the methodological appropriateness of the research design and the strength of evidence for the hypothesis. We illustrate the usefulness of the SEES in providing richer evidence assessment with pilot data from a previous many-analysts study.

Probing the Paradox: Investigating the Impact of Affect, Exercise Type, and Cannabis Use on the Alcohol-Exercise Relationship in College Students.

Alcohol has previously shown a paradoxical positive relationship with exercise behaviors. However, the relationship has not been explored according to type of exercise (aerobic vs. anaerobic), nor has the research considered other contextual variables that commonly co-occur with alcohol use, such as cannabis and mood. This study sought to expand upon previous research to understand how the alcohol-exercise relationship may vary based on exercise type. Additionally, this study included cannabis use and mood as moderators of the alcohol-exercise association. Cross-sectional survey data was collected from college students (N = 335). Negative binomial regression was used to test associations between exercise and alcohol consumption, cannabis use, positive affect (PA), negative affect (NA), and moderating effects of these factors on the alcohol-exercise relationship. Effect sizes are reported from an Incidence Rate Ratio (IRR). Sex assigned at birth (male = 1, female = 0; IRR = 1.34, p = .017), PA (IRR = 1.57, p = .001), and alcohol consumption (IRR = 1.94, p = .037) exhibited positive relationships with exercise. Significant main effects were not observed for negative affect (IRR = 1.17, p = .230), or cannabis use (IRR = 1.00, p = .988). There was a significant interaction between positive affect and alcohol consumption (IRR = 0.87, p = .044) predicting exercise minutes. Alcohol was positively associated with exercise for those with low positive affect (n = 42, b = 12.61, p = .096) and this effect was attenuated as levels of positive affect increased (mean positive affect: n = 232, b = 0.55, p = .926; high positive affect: n = 61, b = -15.86, p = .146). These findings suggest that low positive affect may contribute to the positive link between alcohol use and exercise (especially aerobic exercise) in young people.

Sweet corn phytoglycogen dendrimers as a lyoprotectant for dry-state protein storage.

Protein biotherapeutics typically require expensive cold-chain storage to maintain their fold and function. Packaging proteins in the dry state via lyophilization can reduce these cold-chain requirements. However, formulating proteins for lyophilization often requires extensive optimization of excipients that both maintain the protein folded state during freezing and drying (i.e., "cryoprotection" and "lyoprotection"), and form a cake to carry the dehydrated protein. Here we show that sweet corn phytoglycogens, which are glucose dendrimers, can act as both a protein lyoprotectant and a cake-forming agent. Phytoglycogen (PG) dendrimers from 16 different maize sources (PG1-16) were extracted via ethanol precipitation. PG size was generally consistent at ~70-100 nm for all variants, whereas the colloidal stability in water, protein contaminant level, and maximum density of cytocompatibility varied for PG1-16. 10 mg/mL PG1, 2, 9, 13, 15, and 16 maintained the activity of various proteins, including green fluorescent protein, lysozyme, ß-galactosidase, and horseradish peroxidase, over a broad range of concentrations, through multiple rounds of lyophilization. PG13 was identified as the lead excipient candidate as it demonstrated narrow dispersity, colloidal stability in phosphate-buffered saline, low protein contaminants, and cytocompatibility up to 10 mg/mL in NIH3T3 cell cultures. All dry protein-PG13 mixtures had a cake-like appearance and all frozen protein-PG13 mixtures had a Tg' of ~ -26°C. The lyoprotection and cake-forming properties of PG13 were density-dependent, requiring a minimum density of 5 mg/mL for maximum activity. Collectively these data establish PG dendrimers as a new class of excipient to formulate proteins in the dry state.

Investigating the relationship between changes in metaphysical beliefs and death anxiety following a significant psychedelic experience.

Research examining the potential of the psychedelic experience to alter attitudes toward death is steadily emerging. However, the specific mechanisms leading to this change are not well understood. The present study investigated the potential relationship between changes in metaphysical beliefs and changes in death anxiety following a single significant psychedelic experience. A total of 155 participants completed a retrospective questionnaire that included questions about their acute experience and changes in death anxiety and metaphysical beliefs following a significant psychedelic experience. Although some participants reported an increase in death anxiety, there was an overall significant reduction in death anxiety from before to after the experience. Improvements in death anxiety were positively correlated with changes in belief in panpsychism, but no other measured metaphysical beliefs. The findings from this exploratory study provide direction for future research looking at the relationship between changes in metaphysical beliefs and death anxiety in the context of psychedelic experiences.

Effects of social drinking context on subjective effects, affect, and next-day appraisals in the natural environment.

BACKGROUND: Drinking commonly occurs in social settings and may bolster social reinforcement. Laboratory studies suggest that subjective effects and mood are mechanisms through which the social context influences alcohol consumption. Ecological momentary assessment (EMA) may be useful for extending these findings to the natural environment. This pre-registered secondary analysis of EMA data investigated the influence of the social environment on: (1) stimulating and sedating subjective effects of alcohol, (2) contentedness and negative affect, and (3) next-day evaluations of the drinking occasion. METHODS: Nontreatment seeking adults reporting past-month heavy drinking (N = 131; Mage = 28.09; 42% female) completed 7 days of EMA (in the morning, at random, and following drinking prompts), which included questions on their social context (drinking in the presence of known others or alone), contemporaneous stimulating and sedating effects, contentedness and negative affect, alcohol consumption, and next-day evaluations of a prior day's drinking event (how satisfying/pleasant was drinking). We used multi-level models in SAS 9.4 M7 software to examine relations among the variables. RESULTS: Contemporaneous subjective effects (stimulating or sedating), negative affect, and contentedness did not significantly depend on the social context. For next-day evaluations of pleasure/satisfaction from drinking, context effects were dependent on consumption totals. As the total number of standard drinks consumed increased, recollections of pleasure/satisfaction were higher when drinking had occurred with others, relative to alone. At lower consumption totals, next-day evaluations did not appear to depend on social context. CONCLUSIONS: When reported contemporaneously, subjective effects and affect do not appear dependent upon the presence of known others. However, heavier drinking events, relative to lighter drinking events, are appraised more favorably the following day when occurring within social contexts.

Characterizing the dimensions of positive emotion functioning in young adult alcohol use and alcohol-related problems.

Emotional functioning figures prominently in most contemporary models of alcohol use (Kassel & Veilleux, 2010). These models posit that alcohol use becomes reinforced due to its ability to regulate a person's affect (Sher & Grekin, 2007). A growing body of literature suggests that for youth, positive reinforcement (i.e., using alcohol to enhance positive feelings or to increase their duration) is a leading mechanism facilitating increased use (Emery & Simons 2020; Howard et al., 2015). However, few, if any, studies have examined the unique associations between multiple indicators of positive emotional functioning and alcohol use as well as alcohol-related problems. We aimed to fill this gap by using secondary data from large college student sample (N = 402) to characterize the unique associations between trait indicators of positive emotional functioning (i.e., positive affect, anhedonia, savoring, positive emotion dysregulation) and alcohol use as well as alcohol-related problems. Results indicated trait positive emotion dysregulation (difficulty managing intense positive emotions) was positively related to both alcohol consumption (IRR = 1.03, p =.019) and alcohol-related problems (IRR = 1.03, p =.001). Interestingly, trait savoring (i.e., ability to increase the intensity/duration of positive emotions) was positively related to alcohol consumption (IRR = 1.18, p =.049) and inversely related to problems (IRR = 0.86, p =.019). None of the other positive emotion indicators were significantly associated with either alcohol use or problems.

Temporal associations linking alcohol and cannabis use to cigarette smoking in young adults engaged in a tobacco cessation and relapse monitoring study.

Young adulthood remains a developmental period in which cigarette smoking initiation and progression to dependence and regular use is common. Moreover, co-use of alcohol and/or cannabis with tobacco is common in this age group and may have detrimental effects on tobacco use rates and cessation outcomes. Although young adults are interested in quitting smoking, achieving abstinence remains difficult, even with evidence-based treatment strategies. Understanding proximal associations between other substance use (e.g., alcohol and cannabis) and smoking may have important treatment implications. This exploratory analysis investigated the role of alcohol and/or cannabis use in contributing to smoking events on the same day or next day among young adults engaged in a smoking cessation and relapse monitoring study. We used ecological momentary assessment (EMA) data from 43 young adults (ages 18-25; 932 observations) who smoked cigarettes daily and agreed to participate in a 5-week study that included a 2-day smoking quit attempt and provision of tobacco treatment in the form of nicotine replacement therapy, brief cessation counseling, and financial incentives for abstinence (incentives were provided only during the 2-day quit attempt). We tested multilevel time-series models of daily associations between alcohol use, cannabis use, and smoking. Consistent with hypotheses, days on which participants were more likely to drink alcohol predicted increased likelihood of smoking the next day (OR = 2.27, p =.003). This effect was significant after controlling for both the one-day lagged effect of smoking (i.e., autoregression) and the concurrent (i.e., same day) effects of drinking and cannabis use. Although there was a positive concurrent effect of cannabis use on smoking (OR = 12.86, p =.003), the one-day lagged effect of cannabis use and the concurrent effect of drinking was not significant, contrary to hypotheses. Results indicate that alcohol use presents a potential threat to successful smoking cessation that extends to the following day. This suggests a risk-window in which treatment could be supplemented with just-in-time interventions and extending the focus on co-use to include this lagged impact on cessation outcomes.

Ion binding with charge inversion combined with screening modulates DEAD box helicase phase transitions.

Membraneless organelles, or biomolecular condensates, enable cells to compartmentalize material and processes into unique biochemical environments. While specific, attractive molecular interactions are known to stabilize biomolecular condensates, repulsive interactions, and the balance between these opposing forces, are largely unexplored. Here, we demonstrate that repulsive and attractive electrostatic interactions regulate condensate stability, internal mobility, interfaces, and selective partitioning of molecules both in vitro and in cells. We find that signaling ions, such as calcium, alter repulsions between model Ddx3 and Ddx4 condensate proteins by directly binding to negatively charged amino acid sidechains and effectively inverting their charge, in a manner fundamentally dissimilar to electrostatic screening. Using a polymerization model combined with generalized stickers and spacers, we accurately quantify and predict condensate stability over a wide range of pH, salt concentrations, and amino acid sequences. Our model provides a general quantitative treatment for understanding how charge and ions reversibly control condensate stability.

Examining Associations Between Cannabis Use Disorder and Measures of Weekly and Within-Day Cannabis Frequency, Quantity, and Potency in College Students.

Background: College student cannabis use has increased significantly in recent years, and individuals aged 18-25 are at elevated risk for development of cannabis use disorder (CUD). While weekly cannabis use frequency is a commonly used measure of cannabis consumption, there is increasing scientific interest in exploring more nuanced measures of cannabis use. Currently, limited research exists examining the clinical utility of cannabis quantity, within-day frequency, and potency variables. Methods: We used cross-sectional survey data from a sample of 617 undergraduate students in the state of Colorado. A two-part model-building approach was leveraged to examine whether within-session cannabis quantity and within-day cannabis use frequency were associated with odds of experiencing any CUD symptoms and total number of CUD symptoms endorsed. We also examined whether cannabis flower potency was associated with odds of experiencing any CUD symptoms and total number of CUD symptoms endorsed among a subset (N=288) of the sample who reported knowledge of the cannabinoid content of their most frequently used products. Results: Weekly flower use frequency (odds ratio [OR]=1.27, p<0.001) and weekly concentrate use frequency (OR=1.10, p=0.044) were positively associated with increased odds of experiencing any CUD symptoms, but cannabis quantity and within-day frequency variables were not. In addition, no association was found between flower potency and odds of endorsing any CUD symptoms. Among individuals endorsing at least one symptom, weekly flower use frequency (incident rate ratio [IRR]=1.06, p<0.001) was positively associated with total symptom count, but weekly concentrate use frequency, cannabis quantity variables, and within-day frequency variables were not. Among individuals endorsing symptoms, a positive association was found between flower potency and total symptom count (IRR=1.01, p=0.008). Conclusion: Current methods of assessing within-session cannabis quantity and within-day cannabis use frequency may lack clinical utility in examining college student CUD symptoms over and above weekly cannabis use frequency. Cannabis flower potency may prove useful in assessment of CUD symptom severity, but further research is warranted.

Distinguishing Gender Identity From Biological Sex in Dermatologic Health Care: Methods, Harms, and Paths Forward.

Accurate assessment of gender identity and biological sex in dermatology research is crucial since their conflation or poor demarcation undermines patient respect and study accuracy. Clearer guidance is needed for health care researchers, particularly in light of the notable disparities in skin disease rates, skincare practices, literature representation, and the persistent underrepresentation of transgender and nonbinary patients.

Discrete emotions and global affect: Applying empirically driven approaches to experience sampling data to model state and trait affective structure and affect-alcohol use associations in a heavy drinking young-adult sample.

Affective functioning is central to most contemporary models of alcohol use. However, the affective structure at the within- and between-person levels is rarely investigated nor is the differential predictive value of specific affect dimensions assessed across state and trait formats. We examined a) the structure of state and trait affect using experience sampling methodology (ESM) and b) predictive associations between the empirically derived affect facets and alcohol use. Participants were 92 heavy drinking college students aged 18-25 who completed 8 momentary assessments of their affect and drinking a day for 28-days. We found evidence for a single positive affect factor at both the within- (i.e., state) and between-person (i.e., trait) levels. We found a hierarchical factor structure for negative affect, represented by a general, superordinate dimension as well as facet-level sadness, anxiety, and anger dimensions. Associations between affect and alcohol use differed across trait and state levels and across specific types of negative affect. Lagged state positive affect and sadness as well as trait positive affect and sadness were inversely associated with drinking. Lagged state anxiety and trait general negative affect were positively associated with drinking. Thus, our study demonstrates how associations between drinking and affect can be studied in relation to general (e.g., general negative affect) and more specific aspects of affective experiences (e.g., sadness versus anxiety) concurrently within the same study and across trait and state levels of assessment.

Intersecting sex and American Indian identity moderates school and individual correlates of binge drinking among reservation-area adolescents.

Reservation-area American Indian (AI) youth demonstrate higher rates of binge drinking (BD) than their non-AI peers. However, individual and school-level differences in BD disparities between reservation-area AI/non-AI female and male adolescents remain unexamined. This study applies an Intersectional framework to examine risk and protective factors of BD among reservation-area youth at the intersection of their sex and AI identities. A nationally representative sample of adolescents (N = 14,769; Mage = 14.6, 49% female; 61% AI) attending 103 reservation-serving schools completed a survey between 2015 and 2019. Multilevel modeling was used to examine differences in risk and protective factors of BD between AI and non-AI male and female adolescents. Our findings indicate that the effects of student and school-level risk and protective factors on adolescents' BD are driven primarily by sex within AI and non-AI groups. Implications for future confirmatory research and tailoring school-based prevention programs are discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Mapping environmentally sustainable urban development within six US cities through object-based image change analysis of aerial orthoimagery.

The rapid expansion of cities and continuous urban population growth underscores a need for sustainable urban development. Sustainable development is that which addresses human needs, contributes to well-being, is economically viable, and utilizes natural resources at a degree sustainable by the surrounding environmental systems. Urban green spaces, green roofs, and solar panels are examples of environmentally sustainable urban development (ESUD), or development that focuses on environmental impact, but also presents the potential to achieve social and economic sustainability. The aim of this study was to map and compare amounts of ESUD c. 2010 and c. 2019 through an object-based image analysis (OBIA) approach using National Agricultural Imagery Program (NAIP) aerial orthoimagery for six mid- to large-size cities in the USA. The results of this study indicate a hybrid OBIA and manual interpretation approach applied to NAIP orthoimagery may allow for reliable mapping and areal estimation of urban green space and green roof changes in urban areas. The reliability of OBIA-only mapping and estimation of areal extents of existing green roofs, and new and existing solar panels, is inconclusive due to low mapping accuracy and coarse spatial resolution of aerial orthoimagery relative to some ESUD features. The three urban study areas in humid continental climate zones (Dfa) were estimated to have greater areal extent of new and existing urban green space and existing green roofs, but less areal extent of new green roofs and existing solar panels compared to the three study areas in humid subtropical climate zones (Cfa).

Surgery After BRAF-Directed Therapy Is Associated with Improved Survival in BRAFV600E Mutant Anaplastic Thyroid Cancer: A Single-Center Retrospective Cohort Study.

Background: The aim of this study was to describe the oncologic outcomes of patients with BRAFV600E-mutated anaplastic thyroid cancer (ATC) who had neoadjuvant BRAF-directed therapy with subsequent surgery. For context, we also reviewed patients who received BRAF-directed therapy after surgery, and those who did not have surgery after BRAF-directed therapy. Methods: This was a single-center retrospective cohort study conducted at a tertiary care cancer center in Texas from 2017 to 2021. Fifty-seven consecutive patients with BRAFV600E-mutated ATC and at least 1 month of BRAF-directed therapy were included. Primary outcomes were overall survival (OS) and progression-free survival (PFS). Results: All patients had stage IVB (35%) or IVC (65%) ATC. Approximately 70% of patients treated with BRAF-directed therapy ultimately had surgical resection of residual disease. Patients who had neoadjuvant BRAF-directed therapy followed by surgery (n = 32) had 12-month OS of 93.6% [confidence interval (CI) 84.9-100] and PFS of 84.4% [CI 71.8-96.7]. Patients who had surgery before BRAF-directed therapy (n = 12) had 12-month OS of 74.1% [CI 48.7-99.5] and PFS of 50% [CI 21.7-78.3]. Finally, patients who did not receive surgery after BRAF-directed therapy (n = 13) had 12-month OS of 38.5% [CI 12.1-64.9] and PFS of 15.4% [CI 0-35.0]. Neoadjuvant BRAF-directed therapy reduced tumor size, extent of surgery, and surgical morbidity score. Subgroup analysis suggested that any residual ATC in the surgical specimen was associated with significantly worse 12-month OS and PFS (OS = 83.3% [CI 62.6-100], PFS = 61.5% [CI 35.1-88]) compared with patients with pathologic ATC complete response (OS = 100%, PFS = 100%). Conclusions: We observed that neoadjuvant BRAF-directed therapy reduced extent of surgery and surgical morbidity. While acknowledging potential selection bias, the 12-month OS rate appeared higher in patients who had BRAF-directed therapy followed by surgery as compared with BRAF-directed therapy without surgery; yet, it was not significantly different from surgery followed by BRAF-directed therapy. PFS appeared higher in patients treated with neoadjuvant BRAF-directed therapy relative to patients in the other groups. These promising results of neoadjuvant BRAF-directed therapy followed by surgery for BRAF-mutated ATC should be confirmed in prospective clinical trials.

Emotional Reactions to High-Risk Sex among Sexual Minority Men: Exploring Potential Opportunities for Just-In-Time Intervention.

Rates of HIV and other sexually transmitted infections (STIs) are high among sexual minority men (SMM). A large body of research has explored determinants of HIV/STI risk behavior, but few studies have explored emotional consequences of these events. Understanding the valence, timing, and strength of emotional reactions to sexual risk could inform use of specific behavior change techniques in interventions (such as anticipated regret) and identify new opportunities for intervention, including just-in-time interventions. We analyzed data from an ecological momentary assessment (EMA) study of 100 HIV-negative/unknown-status SMM to understand patterns of positive affect, negative affect, shame, and stress in the 24 hours after sex. Mixed-effects models showed that the probability of negative affect was higher in the hours following condomless anal sex (CAS) with high-risk partners during which SMM reported being under the influence of alcohol or drugs (A/D involved CAS), versus all other types of sex events (OR = 0.92, SE = 0.03, p = .017). The probability of shame was also higher after A/D-involved CAS, versus other sex events (OR = 1.14, SE = 0.07, p = .035). Findings suggest that the hours following A/D-involved CAS events may be an opportune time to intervene to help SMM avoid similarly aversive experiences in the future.

Focusing Narrowly on Model Fit in Factor Analysis Can Mask Construct Heterogeneity and Model Misspecification: Applied Demonstrations across Sample and Assessment Types.

This study builds upon research indicating that focusing narrowly on model fit when evaluating factor analytic models can lead to problematic inferences regarding the nature of item sets, as well as how models should be applied to inform measure development and validation. To advance research in this area, we present concrete examples relevant to researchers in clinical, personality, and related subfields highlighting two specific scenarios when an overreliance on model fit may be problematic. Specifically, we present data analytic examples showing that focusing narrowly on model fit may lead to (a) incorrect conclusions that heterogeneous item sets reflect narrower homogeneous constructs and (b) the retention of potentially problematic items when developing assessment measures. We use both interview data from adult outpatients (N = 2,149) and self-report data from adults recruited online (N = 547) to demonstrate the importance of these issues across sample types and assessment methods. Following demonstrations with these data, we make recommendations focusing on how other model characteristics (e.g., factor loading patterns; carefully considering the content and nature of factor indicators) should be considered in addition to information provided by model fit indices when evaluating factor analytic models.

A Case Report: Lithium-Induced Neurotoxicity, a Differential to Always Consider.

Lithium, a mood stabilizer commonly prescribed for bipolar disorder, has a narrow therapeutic index that increases the risk of toxicity for patients who are prescribed this medication. Patients presenting with lithium toxicity could have a wide array of symptoms triggered by several factors that mimic other neurological conditions. In this paper, we discuss the case of an 81-year-old male who presented to the emergency department with worsening tremors and visual hallucinations, ataxia, and cognitive decline. He was initially thought to have Parkinson's disease with dementia in the outpatient setting and was later found to have lithium toxicity. Swift identification and management, involving fluid diuresis, led to the complete resolution of the patient's neurological symptoms by the fourth day of hospitalization. This case calls attention to the challenges of diagnosing lithium toxicity due to the variability in presentation as well as precipitating factors that clinicians must be cognizant of when working up patients who are prescribed lithium.

Protocol for a mobile laboratory study of co-administration of cannabis concentrates with a standard alcohol dose in humans.

Cannabis is commonly used among people who drink alcohol, yet evidence on acute effects of co-use is conflicting. Two important variables that may influence the effects of cannabis and alcohol are cannabinoid content (i.e., the ratio of cannabidiol [CBD] and 9-tetrahydrocannabinol [THC]) as well as the order of use (i.e., cannabis before alcohol vs. alcohol before cannabis). Research is mixed regarding the acute imapct of cannabis on alcohol consumption and intoxication, with some studies suggesting additive effects of alcohol and cannabis, and others demonstrating negligible effects of combining these substances. Further complicating this, high-THC-content cannabis concentrates are increasingly popular on the legal-market, but to our knowledge, no studies have explored concentrate and alcohol co-use. In addition to cannabinoid content, order of use may influence intoxication and other acute effects, but is also understudied. Co-use studies typically administer a fixed dose of alcohol before cannabis, and there is a lack of data on the acute effects of cannabis before alcohol. Thus, there is a need for experimental co-use studies exploring the impact of cannabinoid content (particularly of highly potent cannabis concentrates) and order effects on intoxication. This study uses a federally-compliant mobile laboratory procedure to explore the effects of co-administration of legal-market cannabis concentrates with a moderate alcohol dose (.8g/kg) in a sample of community participants who regularly use alcohol and cannabis. The study will also explore alcohol and cannabis order effects (cannabis before alcohol vs. alcohol before cannabis). Outcomes are objective intoxication (measured using blood cannabinoid level, heart rate, psychomotor performance and breath alcohol level [BrAC]) and subjective intoxication (assessed via self-report measures). Overall, this study may influence harm-reduction recommendations for individuals who drink alcohol and use cannabis.

Monocyte response after colorectal surgery: A prospective cohort study.

Background: Tumor resection is the common approach in patients with colorectal malignancy. Profound insight into inflammatory changes that accompany the normal post-operative stress response will establish reference parameters useful for identification of putative complications. Alterations in circulating monocytes might be indicative as these cells are considered to be the most responsive leukocytes to trauma. Therefore, the aim of this study is to assess the monocyte subset kinetic and phenotypic changes in response to surgery. Methods: Fifty patients undergoing colorectal tumor resection were included in a multicenter prospective cohort study. Blood samples were collected early in the morning prior to surgery and the next days through postoperative day three for flowcytometric analysis. Leukocyte subtypes were identified and expression of activation stage-related markers by monocyte subsets was quantified. Results: Changes in leukocyte subset composition and monocyte subset phenotypes were most prominent at the first day postoperatively, after which these parameters typically returned to normal or near-normal preoperative values. The immunophenotypic alterations after surgery were most notable in classical and intermediate monocytes. These included up-regulation of activation markers CD64 and CD62L, but down-regulation of HLA-DR and CD54. Markers of de-activation, CD163 and CD206, were consistently increasingly expressed. Discussion/conclusion: The current study gives detailed insight into the peripheral blood leukocyte response after colorectal cancer surgery. This form of short-term stress induces a rapid and significant redistribution of immune cells. Immunophenotypic alterations in monocytes as a response to surgery suggest a mixed profile of cellular activation and de-activation.